Management of malignant germ cell tumours of ovary.

Ten patients of the advanced malignant germ cell tumours of the ovary were treated by cisplatin based combination chemotherapy after initial conservation surgery. Eight patients completed course containing cisplatinum, vinblastine and bleomycin. Five patients (62.5%) achieved CR while 2 (25%) attained PR. One patient died due to tumour lysis and respiratory infection. Rest two patients did not turn up in follow up. Long term follow up indicates above regimen to be highly effective. However poor performance status, advanced stage of disease and post operative gross residual disease were poor prognostic factors in our patients.     

Small-area study of the incidence of neoplasms of the brain and central nervous system among adults in the West Midlands region, 1974-86. Small Area Health Statistics Unit.

This small-area study of incidence of cancers of the brain and central nervous system found evidence of trend (P = 0.02) of cancer risk with deprivation (8% higher risk in affluent areas), but no significant association with urban-rural status. Results were not indicative of a strong geographically determined risk at small-area level.     

Occurrence of malignant non-germ cell components in primary mediastinal germ cell tumours.

METHODS: Thirty-five patients with primary mediastinal germ cell tumours (PMGCT) underwent primary thoracotomy in a 30-year period (1965-1994). Of the 35 patients, 12 had benign teratomas, five pure seminomas and 18 non-seminomatous germ cell tumours. RESULTS: Out of 18 non-seminomatous germ cell tumours, 14 comprised more than one malignant component. In two cases malignant teratomas had an additional malignant non-germ cell component: one a mixed sarcomatous component and the other a neuroendocrinal component. There were different methods of treatment between 1965 and 1994. All but one of patients with seminomas survived for 5 years. Among 18 patients with malignant PMGCT, all but two died within 5 years (mean survival rate was 15 months). CONCLUSIONS: When planning treatment of patients with malignant PMGCT we have to take into account the fact that malignant non-germ-cell components may occur. In this circumstances, surgical resection after initial chemotherapy is recommended.     

Multimodality treatment of malignant germ cell tumours of the mediastinum

Of 15 patients with malignant germ cell tumours of the mediastinum, 9 patients had pure seminomas and 6 had non-seminomas. Resection was radical in only 4 non-seminomas, 1 of which was resected after chemotherapy; radiotherapy was delivered to all seminoma patients as sole therapy (2 patients) or as part of combined modality therapy. All patients with non-seminomatous tumours underwent chemotherapy (cisplatin-based combination). Therapy was generally well tolerated, but 1 seminoma patient died of sepsis. Chemotherapy achieved a 71% complete response rate in pure seminoma patients and a 33% complete response rate in non-seminoma patients. 53% of patients are alive and free of disease beyond 36 months from start of any treatment. Pure seminoma patients survived longer than non-seminoma patients (3 and 5 year survivals were 67% and 33%, respectively). Although cisplatin-based chemotherapy is highly effective in pure seminomas and also in non-seminomas, a better therapeutic approach is needed in non-seminomas.     

'JEB'--a carboplatin based regimen for malignant germ cell tumours in children.

Between February 1986 and July 1988 a total of 21 children aged 1 to 16 years with malignant germ cell tumours (MGCT), 18 with either metastatic disease or unresectable primary tumour, received the JEB regimen - carboplatin dosage calculated from the EDTA glomerular filtration rate (approximately 600 mg m-2), etoposide 120 mg m-2 daily x 3, and bleomycin 15 mg m-2 weekly. Primary sites were: testis (6), ovary (8), sacrococcyx (4), pineal gland (2) and vagina (1). AFP levels were elevated in 19, beta-HCG in 8. Complete marker response was achieved in 19 out of 19 evaluable patients and complete remission of measurable tumour in 16 out of 19, 12 with chemotherapy alone and 4 with the addition of surgery. A reduction in glomerular filtration rate greater than 10% occurred in 3 of 12 evaluable patients; in none greater than 20%. Sequential audiography was normal in 11 out of 12 evaluated. The regimen was myelosuppressive with WHO grade III or IV myelosuppression occurring in 12 patients. Three patients have relapsed; one with a pineal germinoma who relapsed in the abdomen six months after diagnosis, and two with sacrococcygeal teratomas and lung metastases. Two of these remain in second complete remission after further treatment. There was one death from probable bleomycin pulmonary toxicity. We conclude that this regimen is simple to administer and, apart from myelosuppression, it is well tolerated. It appears to have comparable efficacy to cisplatin-based regimens but with much less nephrotoxicity and ototoxicity and avoids the use of alkylating agents and anthracyclines.     

The incidence of advanced breast cancer in the West Midlands, United Kingdom

Breast screening of the West Midlands women of 50-64 years started in 1988. Reductions in breast cancer deaths induced by mammography screening should be preceded by reductions in the incidence of advanced breast cancer. We estimated incidence trends in advanced breast cancer from 1989 to 2004. We extracted numbers of cases of breast cancer found in the West Midlands women aged 50-64 years from the Cancer Incidence in Five Continent database. We used published data for estimating the incidence of advanced breast cancer. Then, annual percent changes in incidence rates were computed using join point regression. The incidence rates of lymph node-positive breast cancer increased from 1989 to 1992. In 1993-1995, they decreased below the prescreening level, but from 1996 to 2000, they returned to prescreening levels and then stabilized. From 1989 to 2004, annual percent changes (95% confidence interval) were 2.2% (1.1-3.2%) for node-negative cancers and -0.7% (-1.9 to 0.4%) for lymph node-positive cancers. The incidence of cancer greater than 50 mm remained stable from 1989 to 2004 [annual percent change: 0.2% (-2.2 to 2.7%)]. Results from the West Midlands suggest that the breast screening program did not play a significant role in reductions in mortality caused by breast cancer.     

Survival of children with malignant germ cell, trophoblastic and other gonadal tumours in Europe

Collaborators of the EUROCARE study had provided records on 1263 cases of germ cell, trophoblastic and other gonadal neoplasms, registered in 34 cancer registries in 16 European countries over the period 1978--1992 and followed-up until the end of 1994. Observed 5-year actuarial survival for 490 cases diagnosed in 1985-1989 was 80% (95% confidence interval (CI)=(76, 83)). The corresponding figures were calculated for the intracranial and intraspinal germ cell tumours (68%, 95% CI=(57, 76)), other non-gonadal germ cell tumours (76%, 95% CI=(68, 82)), gonadal germ-cell tumours (89%, 95% CI=(85, 93)) and gonadal carcinomas (50%, CI=(24, 76)). Relatively large differences in survival were observed between age-sex subgroups, which also differed with histology, with extremely poor survival of young children with intracranial and intraspinal germ cell tumours. Lower survival was observed in the countries with formerly socialist economies. Time trends in survival were examined for the entire study period, including only the cases registered in the large contributing registries. For all germ cell tumours, the risk ratios calculated in the Cox regression analysis were markedly lowered for the years after the reference period of 1978--1981. The improved outcome is attributed to treatment advances.     

Increased mortality rates in young and middle-aged patients with malignant germ cell tumours

Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity. A high incidence of second nongerm cell malignancies is well documented in MGCT survivors. The death risk due to these conditions is, however, more unknown in MGCT patients. Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962 to 1997 aged 相似文献   

Results of treatment of non seminomatous germ cell tumours; 122 consecutive cases in the West of Scotland, 1981-1985

Between January 1981 and December 1985, 122 patients with non-seminomatous germ cell tumours (NSGT) were seen at a regional referral centre. Of these, a total of 98 patients received chemotherapy for metastatic disease. Treatment was given within collaborative EORTC Urology group studies, all of which involved cis-platin-containing schedules. Ninety patients had tumours of testicular origin, and their 2 year actuarial survival rate is 91%; 8 had tumours of extragonadal origin and their 2 year actuarial survival is 25%. Patients with testicular tumours were subdivided by volume of metastatic disease using the recommendations of the Testicular Cancer Subgroup of the MRC Urological Cancer Working Party and survival was significantly worse in the group with very large volume metastatic disease (VLVM, 57%) compared with the groups with large volume metastases (LVM, 100%) and small volume metastases (SVM, 98%). There were 31 patients with Stage I disease at presentation; of these 6 were treated by prophylactic abdominal radiotherapy and 25 were managed by a policy of surveillance only. Seven of these Stage I patients (23%) relapsed with metastatic disease (median 8 months); all have been successfully treated with chemotherapy. These data confirm that the majority of patients now presenting with metastatic NSGCT are curable with chemotherapy, but that a small proportion with very large volume metastases or extragonadal tumours require alternative chemotherapy schedules.     

Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery.

A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy. With a follow-up of 11 to 117 months (median 41 months) all seven patients with seminoma remain alive and disease free giving an overall survival of 100%. Eleven patients had malignant non seminoma; following chemotherapy eight of these had elective surgical resection of residual mediastinal masses. Complete remission was achieved in nine (82%) patients, however, one of these patients died from bleomycin pneumonitis. With a follow-up of 12 to 113 months (median 55 months) eight of 11 (73%) patients with malignant mediastinal teratoma remain alive and disease free.     

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours.

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. 'Progressive disease' included patients who had progressed after a previous partial or complete remission as well as patients who failed primary therapy. Salvage chemotherapy consisted of 'conventional' platinum-based chemotherapy. Prognostic factors for survival were assessed by uni- and multivariate analyses. The resulting prognostic model was validated in an independent data set of 66 similar patients. For all 164 patients the median time from start of induction chemotherapy to progression was 10 months (range: 0-99). Thirty-eight (23%) patients relapsed after 2 years. The 5-year survival rate for all progressing patients was 30% (95% confidence interval 23-38%). In the univariate analysis the following factors most importantly predicted a poor prognosis: progression-free interval < 2 years: initial poor prognosis category (MRC criteria), < CR to induction chemotherapy, initial treatment early in the 1980s and treatment given at a 'small' centre. Three prognostic factors remained in the multivariate analysis: progression-free interval, response to induction treatment and the level of serum human chronic gonadotrophin (hCG) and alpha fetoprotein (AFP) at relapse. One hundred and twenty-four patients could be classified on the basis of these characteristics, Those patients with progression-free interval < 2 years, < CR to induction chemotherapy and high markers at relapse (AFP >100 kU l(-1) or hCG >100 IU l(-1)) formed a poor prognosis group of 30 patients, none of whom survived after 3 years. Patients with at most two of these three risk factors formed a good prognosis group of 94 patients (76%) with a 47% (37-56%) 5-year survival. Thirty-eight patients from the good prognosis group with a progression-free interval of >2 years had a 2-year survival of 74% (60-88%) and 5-year survival of 61%. These prognostic groups were validated in the independent data set, in which 5-year survival rates in the good and poor risk groups were 51% and 0% respectively. One-third of patients progressing during or after platinum-based induction chemotherapy for metastatic germ cell malignancy may be cured by repeated 'conventional' platinum-based chemotherapy. Good prognosis parameters are: progression-free interval of > 2 years, CR to induction treatment and normal or low serum markers at relapse (hCG < 100 IU l(-1) and AFP < 100 kU l(-1)). The results of high-dose salvage chemotherapy should be interpreted on the background of these prognostic factors.     

The epidemiology of non-seminomatous germ cell tumours in the west of Scotland 1975-89.

A total of 438 males resident in the six West of Scotland Health Board areas were notified to the cancer registry with a diagnosis of teratoma between 1 January 1975 and 31 December 1989. Non-registration was between 2% and 3.4%; a further 44 cases were ascertained through independent listings in the major tertiary referral centres. There were four (1%) duplicate registrations and 16 (4%) were incorrect on the basis of pathology (three) or residence (13). Of these, most (26) were registered with alternative diagnoses and eight were registered on the pre-1985 manual system. The positive correlation between socioeconomic status and incidence was confirmed by linking residential postcode at diagnosis to the Carstairs and Morris Deprivation Index. There was an increasing incidence, both overall and for men aged 15-44 years, with doubling times of 20 and 25 years respectively. The increase was confined to men resident in the more deprived postcode sectors; the incidence rate among men from the most affluent areas remained unchanged throughout the period of study.     

Epidemiology of childhood brain tumours in Yorkshire, UK, 1974-95: geographical distribution and changing patterns of occurrence.

From a high-quality population-based register of children with cancer, 455 cases diagnosed with central nervous system (CNS) tumours were analysed to examine patterns of occurrence and geographical distribution. There was a significant increase of 1.8% (95% CI 0.5-3.1, P < 0.01) in average annual incidence for all CNS tumours, mainly accounted for by a 3.1% rise (95% CI 0.1-6.1, P < 0.05) in primitive neuroectodermal tumours (PNETs) over the 22-year period 1974-95. These increases were not explained by an increase in the proportion of histologically verified tumours. In the most recent time period (1986-95), astrocytomas occurred more commonly than previously in 0 to 4-year olds. Geographical differences in incidence were evident at a large scale, between counties, for all tumours and astrocytomas, with lower rates in the most urbanized areas. At the level of census district and electoral wards, no association between incidence of CNS tumours and socioeconomic group, person-based population density or ethnicity was observed using Poisson regression modelling. Based on small-scale census geography, the patterns of distribution of CNS tumours do not suggest strong associations with geographical determinants of risk. This study finds a rising incidence of all CNS tumours and particularly primitive neuroectodermal tumours and shows that astrocytomas appear to be occurring at a younger age, most probably because of improved diagnosis with non-invasive technology.     

Atrophy, hormones, genes and viruses in aetiology germ cell tumours

This chapter reviews the evidence that testicular germ cell atrophy could be the final common pathway for all of the established and postulated risk factors for induction of testis tumours. The evidence from age incidence studies shows that the tumour peak incidence follows the curve of sexual activity in the male, and this provides the starting point for the argument that this tumour is dependent on endocrine factors for its induction. The data from epidemiological studies confirming the high frequency of atrophogenic events and occurrence of low sperm counts in more than 75% of patients provide the principal evidence in support of this hypothesis. The need for more information on hormone sensitivity of this group of tumours and in particular the more differentiated variety, ie seminoma, is highlighted. Information on levels of DNA repair enzyme activity as an explanation of radiosensitivity and chemosensitivity of this group of tumours is also needed. The relationship of HLA linked immune response genes to susceptibility to testicular atrophogenic virus infection needs further investigation, particularly in view of the recent introduction of widespread prepubertal vaccination against mumps virus, one of the most clearly identified testicular atrophogenic viruses. The paper concludes with an examination of the influence of carcinogens and radiation and how they relate to modern ideas of clonal evolution of tumours. The conclusion from this review is that testicular germ cell tumours provide an excellent model of the recent postulate of Ames et al, (1990) that for some cancers mitogenesis might precede mutagenesis, in contrast to the classical view produced from animal models that mutagenic induction is followed by mitogenic promotion.     

Methylator phenotype of malignant germ cell tumours in children identifies strong candidates for chemotherapy resistance

Background:

Yolk sac tumours (YSTs) and germinomas are the two major pure histological subtypes of germ cell tumours. To date, the role of DNA methylation in the aetiology of this class of tumour has only been analysed in adult testicular forms and with respect to only a few genes.

Methods:

A bank of paediatric tumours was analysed for global methylation of LINE-1 repeat elements and global methylation of regulatory elements using GoldenGate methylation arrays.

Results:

Both germinomas and YSTs exhibited significant global hypomethylation of LINE-1 elements. However, in germinomas, methylation of gene regulatory regions differed little from control samples, whereas YSTs exhibited increased methylation at a large proportion of the loci tested, showing a ‘methylator'' phenotype, including silencing of genes associated with Caspase-8-dependent apoptosis. Furthermore, we found that the methylator phenotype of YSTs was coincident with higher levels of expression of the DNA methyltransferase, DNA (cytosine-5)-methyltransferase 3B, suggesting a mechanism underlying the phenotype.

Conclusion:

Epigenetic silencing of a large number of potential tumour suppressor genes in YSTs might explain why they exhibit a more aggressive natural history than germinomas and silencing of genes associated with Caspase-8-dependent cell death might explain the relative resistance of YSTs to conventional therapy.     

Prognosis of malignant sacrococcygeal germ cell tumours according to their natural history and surgical management

IntroductionMalignant sacrococcygeal (SC) germ cell tumours (GCT) may be diagnosed as primary pelvic tumour or malignant recurrence of foetal SC teratoma (FSCT) operated during the neonatal period. In order to evaluate the difference between these two populations, the authors report their experience with SC-GCT registered in the French TGM 95 protocol.Population and methodsThe protocol comprised risk-adapted-chemotherapy (CT) followed by surgery. Standard risk (SR: localized tumour completely resected) had no adjuvant therapy. Intermediate-Risk (IR: localized tumour, incomplete or no initial surgery with αFP<15,000 ng/ml) received Vinblastine–Bleomycin–Cisplatin regimen; while High-Risk (HR: αFP > 15,000 ng/ml and/or metastases) received Etoposide–Ifosfamide–Cisplatin.ResultsFifty-seven patients with SC-GCT, aged 0–80 months (median 16), were registered between 1995 and 2005. Nineteen patients had secondary SC-GCT after FSCT. All patients received CT: 17 IR and 1 SR after reevolution; 39 HR (25 with metastases). 51 patients underwent delayed surgery, which was incomplete in 8 patients.EvolutionSeventy-two percent of the secondary SC-GCT had systematic biological follow-up. αFP increasing was the first presenting sign in 80% of the cases. Patients with secondary SC-GCT had a lower median αFP level at diagnosis, were less frequently classified as HR and received less CT. The two groups with secondary vs. primary SC-GCT had a statistically similar favourable outcome (Overall Survival: 93.8% vs. 86.2%; Event-Free Survival: 89.2 vs. 78.2%; p > 0.34 and >0.32), respectively, but with less burden of therapy.ConclusionsSC-GCT has a good overall prognosis provided complete surgery is achieved and CT is administered to IR and HR patients. SC-GCT in patients followed by αFP after treatment for FSCT had less tumour extension than newly-diagnosed patients, probably because of earlier detection of the disease.     

Burden of testicular, paratesticular and extragonadal germ cell tumours in Europe

We provide updated estimates of survival, incidence, complete prevalence, and proportion cured for patients with testicular/paratesticular and extragonadal germ cell cancers in Europe, grouped according to the new list of cancer types developed by RARECARE. We collected data, archived in European cancer registries, with vital status information available to 31st December 2003. We analysed 26,000 cases of testicular, paratesticular and extragonadal germ cell cancers diagnosed 1995-2002, estimating that about 15,600 new testicular/paratesticular and 630 new extragonadal cancer cases occurred per year in EU27, with annual incidence rates of 31.5/1,000,000 and 1.27/1,000,000, respectively. Slightly more than 436,000 persons were alive at the beginning of 2008 with a diagnosis of testicular/paratesticular cancer, and about 17,000 with a diagnosis of extragonadal germ cell cancer. Five-year relative survival was 96% for testicular/paratesticular cancer and 71% for extragonadal germ cell cancer; the proportions cured were 95% and 69%, respectively. We found limited variation in survival between European regions except for non-seminomatous testicular cancer, for which five-year relative survival ranged from 86% in Eastern Europe to 96% in Northern Europe. Survival for all cancer types considered decreased with increasing age at diagnosis. Further investigation is required to establish the real reasons for the lower survival in Eastern Europe. Considering the high prevalence of these highly curable cancers, it is important to monitor patients long-term, so as to quantify treatment-related risks and develop treatments having limited impact on quality of life.     

Primary malignant mediastinal germ cell tumours: A literature review and a study of 18 cases

From 1957 to 1992, 18 cases of primary mediastinal germ cell tumours were referred to the Peter MacCallum Cancer Institute (PMCI). Six were seminomas, six were mixed germ cell tumours, two were embryonal cell carcinomas, three were teratocarcinomas and one was labelled an ‘anaplastic germ cell tumour’. Two of the 18 patients were female. For seminomas, surgical (and in one case chemotherapeutic) debulking, followed by radiotherapy produced the best results. Mediastinal doses ranged from 30 to 40 Gy. Local control was achieved in those patients receiving mediastinal radiotherapy. Four patients currently survive disease-free. The non-seminomatous germ cell tumours showed a significantly poorer survival, and only two of 12 patients remain alive in remission at 110 and 130 months after diagnosis. Survival has been updated as of November 1997. Attention is focused on the anterior position of the primary germ cell tumours in the mediastinum. A review of the literature up to and including 1997 is presented.